Insufficient information is available to determine rational environmental nitrogen dioxide exposure standards that avoid toxic effects on lung function in normal subjects and patients with pulmonary disorders. Overly lax standards will lead to adverse health effects while too stringent standards result in wasteful expenditures by industry and governmental agencies. We have constructed a controlled environmental chamber that can accurately deliver nitrogen dioxide pollutants of known concentrations for up to 48 hours. Alterations in lung function will be detected by pulmonary function tests (specific airway conductance, forced expiratory flow rates at low lung volumes) that have sufficient sensitivity to detect changes in lung function before symptoms occur. Performance of bronchoalveolar lavage after NO2 exposure permits for the first time assessment of mechanisms of toxicity of these pollutants in humans. Influx of effector cell populations, change in protein content and enzyme activity, and functional activity of alpha-1 proteinase inhibitor will be assessed in lavage fluid after the chamber study. The relationship between NO2 exposure and enhanced susceptibility to infection will be evaluated by studying lavage leukocyte antiviral activity. Data obtained from these studies should permit a better assessment of adeverse health effects from inhalation of nitrogen dioxide. In dogs and normal humans, we will evaluate a technique to assess lung epithelial permeability by the rate of clearance of radiolabelled aerosols from the lung and uptake in the blood. Disappearance from the lung will be measured by a gamma camera. The effect of aerosol size, site of deposition, and lung volume on clearance rates will be determined. Using the methods developed in these studies, normal subjects will be exposed to nitrogen dioxide to determine if clearance of the labelled aerosol can detect altered permeability. Relationships between airway hyperreactivity, airway inflammation, and bronchoalveolar permeability after inhalation of nitrogen dioxide will be evaluated. These studies will determine if external gamma scanning after inhalation of a labelled aerosol is a sensitive means to detect early lung injury.